EP0022922A1 - Method of forming an aqueous dialysis solution - Google Patents
Method of forming an aqueous dialysis solution Download PDFInfo
- Publication number
- EP0022922A1 EP0022922A1 EP80103136A EP80103136A EP0022922A1 EP 0022922 A1 EP0022922 A1 EP 0022922A1 EP 80103136 A EP80103136 A EP 80103136A EP 80103136 A EP80103136 A EP 80103136A EP 0022922 A1 EP0022922 A1 EP 0022922A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- solution
- acid
- concentrate according
- sodium
- cations
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000385 dialysis solution Substances 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title description 7
- 239000000243 solution Substances 0.000 claims abstract description 61
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 34
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 28
- 239000012141 concentrate Substances 0.000 claims abstract description 24
- 239000007864 aqueous solution Substances 0.000 claims abstract description 21
- -1 calcium cations Chemical class 0.000 claims abstract description 18
- 239000011780 sodium chloride Substances 0.000 claims abstract description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 15
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 15
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 10
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 9
- 239000011777 magnesium Substances 0.000 claims abstract description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims abstract description 8
- 239000011575 calcium Substances 0.000 claims abstract description 8
- 239000011591 potassium Substances 0.000 claims abstract description 7
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 7
- 239000011734 sodium Substances 0.000 claims abstract description 7
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- 235000017550 sodium carbonate Nutrition 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 239000007792 gaseous phase Substances 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 159000000003 magnesium salts Chemical class 0.000 claims description 2
- 239000001103 potassium chloride Substances 0.000 claims description 2
- 235000011164 potassium chloride Nutrition 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract description 7
- 230000003385 bacteriostatic effect Effects 0.000 abstract description 3
- 159000000007 calcium salts Chemical class 0.000 abstract description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 17
- 229910002092 carbon dioxide Inorganic materials 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000003513 alkali Substances 0.000 description 8
- 239000001569 carbon dioxide Substances 0.000 description 8
- 229940001593 sodium carbonate Drugs 0.000 description 7
- 208000010444 Acidosis Diseases 0.000 description 4
- 230000007950 acidosis Effects 0.000 description 4
- 208000026545 acidosis disease Diseases 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 235000011160 magnesium carbonates Nutrition 0.000 description 2
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229940043430 calcium compound Drugs 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical class [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 150000002681 magnesium compounds Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000011182 sodium carbonates Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1654—Dialysates therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Definitions
- haemo dialysis solutions which contain sodium bicarbonate together with sodium chloride and optionally other alkali and alkali earth chlorides. But there has been found as disadvantage of such dialysis solutions containing bicarbonate that calcium and magnesium carbonates may precipitate. In order to avoid these disadvantages, different methods have been used. One method was to replace sodium acetate for the bicarbonate since the alkali earth acetates are easily soluble, so that no precipitates of slightly soluble calcium or magnesium compounds result. But since the acetate is partly transferred into the blood, sometimes the patients show acidosis which makes undesirable the use of acetate instead of bicarbonate in haemo dialysis solutions.
- Another method was that, to bubble carbon dioxide into the dialysis solution in order to maintain the pH value of the dialysis solution in the acidic range and to suppress the formation of slightly soluble magnesium and calcium carbonates. But bubbling carbon dioxide into a dialysis solution is a process complicated and capable of interferences, and in this method the introduced amount of carbon dioxide and thus the pH value can be controlled only relatively bad.
- concentrates for dialysis solutions which concentrates have only to be diluted by water to become useful. But concentrates of aqueous sodium bicarbonate solutions containing calcium ions are not stable and only slightly bacteriostatic.
- the object of the invention was to obtain concentrates for dialysis solutions which are storable and bacteriostatic, also in their final composition, and thus may be left standing for some time without the necessity of bubbling carbon dioxide into the solution. Moreover the dialysis solutions shall contain at most slow amounts of acetate.
- the inventive aqueous concentrate for dialysis solutions containing sodium chloride, carbonate or hydrocarbonate, respectively, calcium cations and optionally magnesium and/or potassium cations is characterized in that it is divided to two containers one of which contains an aqueous solution (A) of sodium carbonate or bicarbonate and the other of which contains an aqueous solution (B) of the calcium cations and, if magnesium cations are contained, of the magnesium cations,as well as of an acid which forms physiologically compatible sodium, calcium and optionally potassium and magnesium salts.
- the solution (A) contains sodium carbonate and the solution (B) contains hydrochloric acid as the acid.
- the hydrochloric acid contained in the solution (B) serves on the one hand completely to convert the sodium carbonate to sodium bicarbonate and on the other hand to decompose a smaller portion of the formed sodium bicarbonate forming carbon dioxide, it is; preferred that the solution (B) contains 1,05 to 1,3, preferably 1,05 to 1,2 mole of HC1 per mole of Na 2 CO 3 in the solution (A).
- One mole of the said hydrochloric acid i s necessary to convert quantitatively the sodium carbon ate to sodium bicarbonate, whereas the remaining amoun t of hydrochloric acid serves to release CO 2 .
- the amount of sodium chloride formed duriung the said reactions may be calculated, so that there is added to the solutions (A) and/or (B) the amount of sodium chloride necessary for the dialysis solution, less the amount of sodium chloride formed in the above reactions.
- the said sodium chloride which is necessary in the dialysis solution to make it substantially isotonic with the blood liquid may be added to each of the both solutions (A) and (B) or partially to both. Additionally there are added calcium chloride and optionally magnesium chloride and potassium chloride to the concentrate in the usual manner.
- the amounts of these compounds in the dialysis solutions are known and are not distinguished from the prior art.
- the solution (A) may be used as standard stock solution for solutions (B) halving different concentration, if only the concentration of hydrochloric acid thereof is in conformity with the concomtration of sodium carbonate in the solution (A) corresponding to the above statements.
- the solution (A) cont ains sodium bicarbonate.
- aqueous solution (A) sodium bicarbonate solutions designated as aqueous solution (A) are stable during long time storage and result in stabel dialysis solutions without bubbling carbon dioxide into the solutions to stabilize them.
- the ready dialysis solution may contain only small amounts of alkali acetate which do not result in acidosis.
- the aqueous solution (B) contains 0,01 to 0,25, especially 0,03 to 0,15, such as for example about 0,05 mole of the stated acid per mole of sodium bicarbonate in the aqueous solution (A).
- the hydrogen ions react with a small part of the sodium bicarbonate forming C0 2 which remains in the dialysis solution and stabilizes it by avoiding a formation of alkali earth carbonates and by adjusting the pH value of the dialysis solution.
- inorganic or organic acids may be used, which form physiologically compatible sodium and calcium salts and, if the aqueous concentrates contain magnesium and potassium cations, form physiologically compatible magnesium and potassium salts, too.
- acids which may be used according to the invention are for example acetic acid, citric acid, lactic acid, hydrochloric acid and/or amino acids.
- Acetic acid is preferred among the said acids, if sodium bicarbonate is used in the solution (A).
- the said acetic acid may be used without hesitation, since the amount thereof is relatively small in comparison with the amount of hydrocarbonate, so that from the dialysis solution only neglectible amounts of acetate can be transferred into the blood of the patient, so that no risk of acidosis exists.
- the sodium chloride may be contained in both aqueous solutions (A) and/or (B), but it is preferably present in the solution (A) in a concentration as high as possible.
- the sodium chloride increases the autosterilityofthe aqueous solutions. If the aqueous solution (A) contains a great portion of sodium cations, by different dosage of the relative amount of the solution (A) at the combination with the solution (B) and with dilution water, optional millival values for the sodium in the dialysis solution may be adjusted without having stock solutions of different concentrations. That by the superdosage or underdosage relating to the solution (A) also the other components, such as sodium bicarbonate, are super or under dosed, is no disadvantage , since the bicarbonate is rapidly decomposed by the body.
- the aqueous solution (B) contains additionally glucose.
- the amount of the glucose in the solution (B) is suitably 5 to 400 gs/1, preferably 15 to 80 gs/l.
- An increased storage stability of the concentrates according to the invention is obtained, if the solution (A) is maintained in a container and under such conditions, that no or only small escape of C0 2 from the solution and the gaseous phase above the said solution out of the said container is possible.
- the container can be manufactured of a material or with such a thickness of the wall that no C0 2 or only a very small amount of C02 escapes from the solution through the wall of the container.
- Another suitable method is to store the solution (A) in comparably big containers, so that the ratio of the volume to the surface area of the liquid body is relatively great. Thereby the interface between the solution and the wall of the container, where C0 2 may escape by diffusion, is relatively small in comparison with the volume of the solution.
- aqueous concentrates for dialysis solutions according to the invention have several important advantages over known concentrates for the same purpose.
- a first advantage is that the solutions are completely stable at the storage during a long period of time as well as at a longer storage during the use without the precipitation of slightly soluble alkali earth compounds and without turbidity.
- Another advantage is that by the concentrates according to the invention dialysis solutions are obtained which do not result in any physiological disadvantage such as acidosis.
- both aqueous solutions (A) and (B) are mixed together and with the dilution water separately from the dialysis device or within the dialysis device immediately before the membrane, whereby suitably the solution (A) is diluted with water and then the solution (B) is metered.
- This may be done suitably by forced dosage in order to adjust the correct ratio of both solutions (A) and (B), whereby in the mixing device the solution obtains the necessary tempereature.
- a conductivity and optionally a pH value, density- and/or flow control device may be provided.
- the feed of the solutions (A) and/or (B) may be made dependent from the above mentioned measured values, and by these measurements the feed may be controlled.
Landscapes
- Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- External Artificial Organs (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
Description
- It is known to use haemo dialysis solutions which contain sodium bicarbonate together with sodium chloride and optionally other alkali and alkali earth chlorides. But there has been found as disadvantage of such dialysis solutions containing bicarbonate that calcium and magnesium carbonates may precipitate. In order to avoid these disadvantages, different methods have been used. One method was to replace sodium acetate for the bicarbonate since the alkali earth acetates are easily soluble, so that no precipitates of slightly soluble calcium or magnesium compounds result. But since the acetate is partly transferred into the blood, sometimes the patients show acidosis which makes undesirable the use of acetate instead of bicarbonate in haemo dialysis solutions. Another method was that, to bubble carbon dioxide into the dialysis solution in order to maintain the pH value of the dialysis solution in the acidic range and to suppress the formation of slightly soluble magnesium and calcium carbonates. But bubbling carbon dioxide into a dialysis solution is a process complicated and capable of interferences, and in this method the introduced amount of carbon dioxide and thus the pH value can be controlled only relatively bad.
- Additionally the physicians prefer storable concentrates for dialysis solutions which concentrates have only to be diluted by water to become useful. But concentrates of aqueous sodium bicarbonate solutions containing calcium ions are not stable and only slightly bacteriostatic.
- The object of the invention was to obtain concentrates for dialysis solutions which are storable and bacteriostatic, also in their final composition, and thus may be left standing for some time without the necessity of bubbling carbon dioxide into the solution. Moreover the dialysis solutions shall contain at most slow amounts of acetate.
- The inventive aqueous concentrate for dialysis solutions containing sodium chloride, carbonate or hydrocarbonate, respectively, calcium cations and optionally magnesium and/or potassium cations is characterized in that it is divided to two containers one of which contains an aqueous solution (A) of sodium carbonate or bicarbonate and the other of which contains an aqueous solution (B) of the calcium cations and, if magnesium cations are contained, of the magnesium cations,as well as of an acid which forms physiologically compatible sodium, calcium and optionally potassium and magnesium salts.
- According to the first embodiment of the invention the solution (A) contains sodium carbonate and the solution (B) contains hydrochloric acid as the acid.
- It is unusual to use strong acids such as hydrochloric acid in physiological aqueous solutions;. But the said acid is immediately reacted when combimed with the aqueous solution containing the sodium carbonate, whereby sodium chloride is formed. During that reaction the sodium carbonate forms the equivalent amount of sodium bicarbonate, and in the event of a corresponding proportionstion of the amount of hydrochlorid acid, a smaller part of the said sodium bicarbonate is decomposed to form additional sodium chloride and carbon dioxide which has the function of the carbon dioxide which is usually bubbled into the solution and adjusts the pH value of the dialysi.s solution.
- Thus since the hydrochloric acid contained in the solution (B) serves on the one hand completely to convert the sodium carbonate to sodium bicarbonate and on the other hand to decompose a smaller portion of the formed sodium bicarbonate forming carbon dioxide, it is; preferred that the solution (B) contains 1,05 to 1,3, preferably 1,05 to 1,2 mole of HC1 per mole of Na2CO3 in the solution (A). One mole of the said hydrochloric acid i s necessary to convert quantitatively the sodium carbon ate to sodium bicarbonate, whereas the remaining amoun t of hydrochloric acid serves to release CO2.
- The amount of sodium chloride formed duriung the said reactions may be calculated, so that there is added to the solutions (A) and/or (B) the amount of sodium chloride necessary for the dialysis solution, less the amount of sodium chloride formed in the above reactions. The said sodium chloride which is necessary in the dialysis solution to make it substantially isotonic with the blood liquid, may be added to each of the both solutions (A) and (B) or partially to both. Additionally there are added calcium chloride and optionally magnesium chloride and potassium chloride to the concentrate in the usual manner. The amounts of these compounds in the dialysis solutions are known and are not distinguished from the prior art. However, it is suitable to have in the solution (A) only sodium carbonates, but in the solution (B) additionally to the hydrochloric acid all other compounds, since then the solution (A) may be used as standard stock solution for solutions (B) halving different concentration, if only the concentration of hydrochloric acid thereof is in conformity with the concomtration of sodium carbonate in the solution (A) corresponding to the above statements.
- Since smaller a'mounts of acetate are not dangereous, it is also possible to replace acetic acid for a smaller portion of the hydrochloric acid.
- For example per mole of sodium carbonate in the solution (A) 1 mole of HCl and 0,05 to O,3 mole of acetic acid should be present in the solution (B).
- According to a second embodiment of the invention the solution (A) cont ains sodium bicarbonate.
- It is surpris ing that the sodium bicarbonate solutions designated as aqueous solution (A) are stable during long time storage and result in stabel dialysis solutions without bubbling carbon dioxide into the solutions to stabilize them.
- For this effecst it is sufficient that only relatively small amounts of art acid which forms the stated physiologically competable alkali and alkali earth salts are used. This results in the advantage for example in the event of the use of acetic acid, that the ready dialysis solution may contain only small amounts of alkali acetate which do not result in acidosis. Preferably the aqueous solution (B) contains 0,01 to 0,25, especially 0,03 to 0,15, such as for example about 0,05 mole of the stated acid per mole of sodium bicarbonate in the aqueous solution (A).
- By the combination of the two solutions (A) and (B) and with dilution water the hydrogen ions react with a small part of the sodium bicarbonate forming C02 which remains in the dialysis solution and stabilizes it by avoiding a formation of alkali earth carbonates and by adjusting the pH value of the dialysis solution.
- As acid in the aqueous solution (B) inorganic or organic acids may be used, which form physiologically compatible sodium and calcium salts and, if the aqueous concentrates contain magnesium and potassium cations, form physiologically compatible magnesium and potassium salts, too. Such acids which may be used according to the invention are for example acetic acid, citric acid, lactic acid, hydrochloric acid and/or amino acids.
- Acetic acid is preferred among the said acids, if sodium bicarbonate is used in the solution (A). The said acetic acid may be used without hesitation, since the amount thereof is relatively small in comparison with the amount of hydrocarbonate, so that from the dialysis solution only neglectible amounts of acetate can be transferred into the blood of the patient, so that no risk of acidosis exists.
- The sodium chloride may be contained in both aqueous solutions (A) and/or (B), but it is preferably present in the solution (A) in a concentration as high as possible. The sodium chloride increases the autosterilityofthe aqueous solutions. If the aqueous solution (A) contains a great portion of sodium cations, by different dosage of the relative amount of the solution (A) at the combination with the solution (B) and with dilution water, optional millival values for the sodium in the dialysis solution may be adjusted without having stock solutions of different concentrations. That by the superdosage or underdosage relating to the solution (A) also the other components, such as sodium bicarbonate, are super or under dosed, is no disadvantage , since the bicarbonate is rapidly decomposed by the body.
- It may be suitable, if the aqueous solution (B) contains additionally glucose. The amount of the glucose in the solution (B) is suitably 5 to 400 gs/1, preferably 15 to 80 gs/l.
- An increased storage stability of the concentrates according to the invention is obtained, if the solution (A) is maintained in a container and under such conditions, that no or only small escape of C02 from the solution and the gaseous phase above the said solution out of the said container is possible. This may be reached in a different manner. For example the container can be manufactured of a material or with such a thickness of the wall that no C02 or only a very small amount of C02 escapes from the solution through the wall of the container. Another suitable method is to store the solution (A) in comparably big containers, so that the ratio of the volume to the surface area of the liquid body is relatively great. Thereby the interface between the solution and the wall of the container, where C02 may escape by diffusion, is relatively small in comparison with the volume of the solution. This is especially important, if for the storage of the solution plastic containers must be used for which a diffusion of C02 through the wall of the container cannot be excluded. It is surprising that by the choice of big storage containers the bicarbonate solution (A) remains completely stable for long periods of time. The stability of the said solution can still be improved by a storage at low temperatures.
- In a surprising manner the solutions are unstable, if they contain too much unbound CO2at the time of filling into the containers, since then the containers inflate. This is avoided by the invention.
- The aqueous concentrates for dialysis solutions according to the invention have several important advantages over known concentrates for the same purpose. A first advantage is that the solutions are completely stable at the storage during a long period of time as well as at a longer storage during the use without the precipitation of slightly soluble alkali earth compounds and without turbidity.
- Another advantage is that by the concentrates according to the invention dialysis solutions are obtained which do not result in any physiological disadvantage such as acidosis.
- Finally a high autosterility and a good flexibility of the dosage are obtained, so that optional sodium concentrations in the dialysis solution may be adjusted without having stock solutions of different concentration.
- In the practical use both aqueous solutions (A) and (B) are mixed together and with the dilution water separately from the dialysis device or within the dialysis device immediately before the membrane, whereby suitably the solution (A) is diluted with water and then the solution (B) is metered. This may be done suitably by forced dosage in order to adjust the correct ratio of both solutions (A) and (B), whereby in the mixing device the solution obtains the necessary tempereature. Moreover as safety precaution a conductivity and optionally a pH value, density- and/or flow control device may be provided. If desired, the feed of the solutions (A) and/or (B) may be made dependent from the above mentioned measured values, and by these measurements the feed may be controlled.
-
- Solution (A):
- water 1 1
- NaHC03 132,3 gs (1575 mmole)
- sodium chloride 61,36 gs (1050 mmole)
- filling up with water to a total volume of 2 1
- Solution (B):
- water 0,5 1
- acetic acid 10,517 gs (175 mmole)
- NaCl 122,72 gs (2100 mmole)
- KC1 5,227 gs (70 mmole)
- MgCl2.6H2O 7,116 gs (35 mmole)
- CaC12.6H20 13,42 gs (61,25 mmole)
- filling up with water to a total volume of 1 1
- During the combination of both aqueous solutions there has been diluted with 32 1 of water to totally 35 1 of dialysis solution. This solution contained 5 mmole C02, and in a surprising manner this amount was sufficient to maintain the dialysis solution stable during storage for a longer time, too.
-
- Solution (A):
- Water 1000 1
- Na2CO3 water-free 211,47 kg
- filling up with water to a total volume of 1500 1
- Solution (B):
- water 750 1
- NaCl 181,0 kg HC1, 37%ig, 212,1 kg
- MgCl2.6H2O 10,674 kg
- -CaCl2.6H2O 20,13 kg
- filling up with water to a total volume of 1500 1
Claims (11)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT80103136T ATE3241T1 (en) | 1979-07-24 | 1980-06-06 | PROCEDURE FOR PREPARING AN AQUEOUS DIALYSIS SOLUTION. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2929871A DE2929871A1 (en) | 1979-07-24 | 1979-07-24 | AQUEOUS CONCENTRATE FOR DIALYSIS SOLUTIONS |
DE2929871 | 1979-07-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0022922A1 true EP0022922A1 (en) | 1981-01-28 |
EP0022922B1 EP0022922B1 (en) | 1983-05-11 |
Family
ID=6076569
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP80103136A Expired EP0022922B1 (en) | 1979-07-24 | 1980-06-06 | Method of forming an aqueous dialysis solution |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0022922B1 (en) |
JP (1) | JPS5620511A (en) |
AT (1) | ATE3241T1 (en) |
DE (2) | DE2929871A1 (en) |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0086553A1 (en) * | 1982-01-29 | 1983-08-24 | Preston Leonard Veltman | Dialysis solutions containing bicarbonate ions |
WO1985001657A1 (en) * | 1983-10-07 | 1985-04-25 | The State Of Victoria | Treatment of animal diarrhoea |
EP0161471A2 (en) * | 1984-04-06 | 1985-11-21 | Fresenius AG | Holder for a fluid containing bicarbonate |
US4762618A (en) * | 1985-06-04 | 1988-08-09 | Gambro Ab | Apparatus and method for controlling fluid flow in dialysis and the like |
US4784495A (en) * | 1987-02-06 | 1988-11-15 | Gambro Ab | System for preparing a fluid intended for a medical procedure by mixing at least one concentrate in powder form with water |
EP0399549A1 (en) * | 1989-05-26 | 1990-11-28 | Fresenius AG | Hydrous concentrate containing sodium bicarbonate and CAPD-bag system with two chambers |
EP0457960A2 (en) * | 1990-05-17 | 1991-11-27 | Minntech Corporation | High acid concentration dialysates |
DE4122754A1 (en) * | 1991-07-10 | 1993-01-21 | Martin Prof Dr Med Vlaho | Substitute soln. for haemo-filtration in dialysing processes - contains sodium, potassium, calcium, magnesium, chloride ions, glucose, lactate and bi:carbonate, esp. for patients with weakened liver function |
EP0564672A1 (en) * | 1992-04-06 | 1993-10-13 | Baxter International Inc. | Aqueous solution for peritoneal dialysis |
DE4211455C1 (en) * | 1992-04-06 | 1993-12-16 | Schael Wilfried | Continuous prepn. of blod dialysis fluids - uses precise concns. of aq. concentrates tailored to patient's requirements |
EP0613688A1 (en) * | 1993-02-19 | 1994-09-07 | Wilfried Dr.-Ing. Schäl | Process for preparing a bicarbonate containing dialysis liquid for the hemodialysis |
US5827820A (en) * | 1992-04-06 | 1998-10-27 | Baxter International Inc. | Aqueous peritoneal dialysis solution |
EP1056491A1 (en) * | 1998-02-19 | 2000-12-06 | Vasca, Inc. | Hemofiltration system including ultrafiltrate purification and re-infusion system |
EP0602014B2 (en) † | 1989-05-26 | 2001-10-10 | Terumo Kabushiki Kaisha | Preparation for blood dialysis and method for production thereof |
EP1721606A2 (en) | 1998-10-20 | 2006-11-15 | Advanced Renal Technologies | Buffered compositions for dialysis |
US7670491B2 (en) | 1998-10-20 | 2010-03-02 | Advanced Renal Technologies | Buffered compositions for dialysis |
US7837666B2 (en) | 2005-01-28 | 2010-11-23 | Fresenius Medical Care North America | Systems and methods for delivery of peritoneal dialysis (PD) solutions |
US7862530B2 (en) | 1999-09-22 | 2011-01-04 | Advanced Renal Technologies | High citrate dialysate and uses thereof |
US9585810B2 (en) | 2010-10-14 | 2017-03-07 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3224823A1 (en) * | 1982-07-02 | 1984-01-05 | Lentia GmbH Chem. u. pharm. Erzeugnisse - Industriebedarf, 8000 München | Process for the preparation of an electrolyte solution, which is optimised for the particular patient, for use in haemodialysis |
US4655941A (en) * | 1984-02-13 | 1987-04-07 | Tomita Pharmaceutical Corp., Ltd. | Method of preparing mixed electrolyte powder for bicarbonate dialysis and powder mixture formed |
JPS6122865A (en) * | 1984-07-11 | 1986-01-31 | 扶桑薬品工業株式会社 | Replenishing solution for artificial kidney apparatus |
US6770148B1 (en) | 1998-12-04 | 2004-08-03 | Baxter International Inc. | Peritoneal dialysis solution containing modified icodextrins |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR1546072A (en) * | 1967-11-27 | 1968-11-15 | Lucas Industries Ltd | Hemodialysis facility |
US3525686A (en) * | 1968-03-19 | 1970-08-25 | American Hospital Supply Corp | Hemodialysis solution containing sorbitol and method of using same |
US3560380A (en) * | 1968-10-28 | 1971-02-02 | Mallinckrodt Chemical Works | Dry concentrates for preparing hemodialysis solutions |
GB1368566A (en) * | 1972-04-05 | 1974-10-02 | Vnii Khirurgicheskoi Apparatur | Device for preparation of dialyzing solution |
FR2237639A1 (en) * | 1973-07-20 | 1975-02-14 | Gensollen Yves | Degasser for artificial kidney dialysis liquid - senses growing gas vol. in degasser to actuate connection with vacuum system |
FR2271864A1 (en) * | 1973-09-26 | 1975-12-19 | Sorin Spa | Mixing chamber for coagulating fluids - having non-clogging characteristics |
US4085046A (en) * | 1976-08-16 | 1978-04-18 | Saporito Jr Thomas J | Renal dialysis concentrate delivery system |
US4136708A (en) * | 1977-06-08 | 1979-01-30 | Renal Systems, Inc. | Hemodialysate blending system |
-
1979
- 1979-07-24 DE DE2929871A patent/DE2929871A1/en not_active Withdrawn
-
1980
- 1980-06-06 AT AT80103136T patent/ATE3241T1/en active
- 1980-06-06 DE DE8080103136T patent/DE3063088D1/en not_active Expired
- 1980-06-06 EP EP80103136A patent/EP0022922B1/en not_active Expired
- 1980-07-23 JP JP10104380A patent/JPS5620511A/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR1546072A (en) * | 1967-11-27 | 1968-11-15 | Lucas Industries Ltd | Hemodialysis facility |
US3525686A (en) * | 1968-03-19 | 1970-08-25 | American Hospital Supply Corp | Hemodialysis solution containing sorbitol and method of using same |
US3560380A (en) * | 1968-10-28 | 1971-02-02 | Mallinckrodt Chemical Works | Dry concentrates for preparing hemodialysis solutions |
GB1368566A (en) * | 1972-04-05 | 1974-10-02 | Vnii Khirurgicheskoi Apparatur | Device for preparation of dialyzing solution |
FR2237639A1 (en) * | 1973-07-20 | 1975-02-14 | Gensollen Yves | Degasser for artificial kidney dialysis liquid - senses growing gas vol. in degasser to actuate connection with vacuum system |
FR2271864A1 (en) * | 1973-09-26 | 1975-12-19 | Sorin Spa | Mixing chamber for coagulating fluids - having non-clogging characteristics |
US4085046A (en) * | 1976-08-16 | 1978-04-18 | Saporito Jr Thomas J | Renal dialysis concentrate delivery system |
US4136708A (en) * | 1977-06-08 | 1979-01-30 | Renal Systems, Inc. | Hemodialysate blending system |
Cited By (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4489535A (en) * | 1980-10-02 | 1984-12-25 | Veltman Preston Leonard | Materials and method for preparing dialysis solutions containing bicarbonate ions |
EP0086553A1 (en) * | 1982-01-29 | 1983-08-24 | Preston Leonard Veltman | Dialysis solutions containing bicarbonate ions |
WO1985001657A1 (en) * | 1983-10-07 | 1985-04-25 | The State Of Victoria | Treatment of animal diarrhoea |
EP0161471A2 (en) * | 1984-04-06 | 1985-11-21 | Fresenius AG | Holder for a fluid containing bicarbonate |
EP0161471A3 (en) * | 1984-04-06 | 1987-06-24 | Fresenius Ag | Holder for a fluid containing bicarbonate |
US4762618A (en) * | 1985-06-04 | 1988-08-09 | Gambro Ab | Apparatus and method for controlling fluid flow in dialysis and the like |
US4784495A (en) * | 1987-02-06 | 1988-11-15 | Gambro Ab | System for preparing a fluid intended for a medical procedure by mixing at least one concentrate in powder form with water |
DE3917251A1 (en) * | 1989-05-26 | 1990-11-29 | Fresenius Ag | Sodium biscarboxylate-containing concentrate and method for producing a dihydrogenation liquid |
EP0602014B2 (en) † | 1989-05-26 | 2001-10-10 | Terumo Kabushiki Kaisha | Preparation for blood dialysis and method for production thereof |
US5211643A (en) * | 1989-05-26 | 1993-05-18 | Fresenius Ag | Sodium bicarbonate containing precipitate-free dialysis solutions |
EP0399549A1 (en) * | 1989-05-26 | 1990-11-28 | Fresenius AG | Hydrous concentrate containing sodium bicarbonate and CAPD-bag system with two chambers |
EP0457960A2 (en) * | 1990-05-17 | 1991-11-27 | Minntech Corporation | High acid concentration dialysates |
EP0457960A3 (en) * | 1990-05-17 | 1993-01-07 | Minntech Corporation | High acid concentration dialysates |
DE4122754A1 (en) * | 1991-07-10 | 1993-01-21 | Martin Prof Dr Med Vlaho | Substitute soln. for haemo-filtration in dialysing processes - contains sodium, potassium, calcium, magnesium, chloride ions, glucose, lactate and bi:carbonate, esp. for patients with weakened liver function |
EP0564672A1 (en) * | 1992-04-06 | 1993-10-13 | Baxter International Inc. | Aqueous solution for peritoneal dialysis |
WO1993019792A1 (en) * | 1992-04-06 | 1993-10-14 | Baxter Deutschland Gmbh | Aqueous peritoneal dialysis solution |
DE4211455C1 (en) * | 1992-04-06 | 1993-12-16 | Schael Wilfried | Continuous prepn. of blod dialysis fluids - uses precise concns. of aq. concentrates tailored to patient's requirements |
US5827820A (en) * | 1992-04-06 | 1998-10-27 | Baxter International Inc. | Aqueous peritoneal dialysis solution |
EP0613688A1 (en) * | 1993-02-19 | 1994-09-07 | Wilfried Dr.-Ing. Schäl | Process for preparing a bicarbonate containing dialysis liquid for the hemodialysis |
EP1056491A1 (en) * | 1998-02-19 | 2000-12-06 | Vasca, Inc. | Hemofiltration system including ultrafiltrate purification and re-infusion system |
EP1056491A4 (en) * | 1998-02-19 | 2004-04-21 | Nxstage Medical Inc | Hemofiltration system including ultrafiltrate purification and re-infusion system |
EP1721606A2 (en) | 1998-10-20 | 2006-11-15 | Advanced Renal Technologies | Buffered compositions for dialysis |
EP1721606A3 (en) * | 1998-10-20 | 2009-06-17 | Advanced Renal Technologies | Buffered compositions for dialysis |
US7670491B2 (en) | 1998-10-20 | 2010-03-02 | Advanced Renal Technologies | Buffered compositions for dialysis |
US9216247B2 (en) | 1998-10-20 | 2015-12-22 | Advanced Renal Technologies | Buffered compositions for dialysis |
US8864699B2 (en) | 1999-09-22 | 2014-10-21 | Advanced Renal Technologies | High citrate dialysate and uses thereof |
US7862530B2 (en) | 1999-09-22 | 2011-01-04 | Advanced Renal Technologies | High citrate dialysate and uses thereof |
US7837666B2 (en) | 2005-01-28 | 2010-11-23 | Fresenius Medical Care North America | Systems and methods for delivery of peritoneal dialysis (PD) solutions |
US8052631B2 (en) | 2005-01-28 | 2011-11-08 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions |
US8328784B2 (en) | 2005-01-28 | 2012-12-11 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions |
US7985212B2 (en) | 2005-01-28 | 2011-07-26 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions |
US9180069B2 (en) | 2005-01-28 | 2015-11-10 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions |
US7935070B2 (en) | 2005-01-28 | 2011-05-03 | Fresenius Medical Care North America | Systems and methods for dextrose containing peritoneal dialysis (PD) solutions with neutral pH and reduced glucose degradation product |
US9585810B2 (en) | 2010-10-14 | 2017-03-07 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser |
US10842714B2 (en) | 2010-10-14 | 2020-11-24 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter chamber diffuser |
US11779519B2 (en) | 2010-10-14 | 2023-10-10 | Fresenius Medical Care Holdings, Inc. | Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser |
Also Published As
Publication number | Publication date |
---|---|
ATE3241T1 (en) | 1983-05-15 |
JPS5620511A (en) | 1981-02-26 |
DE3063088D1 (en) | 1983-06-16 |
DE2929871A1 (en) | 1981-01-29 |
EP0022922B1 (en) | 1983-05-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0022922B1 (en) | Method of forming an aqueous dialysis solution | |
EP0417478B2 (en) | Sodium bicarbonate containing mixture for producing a dialysis solution | |
CA2250819C (en) | Solution for transperitoneal dialysis | |
US4931305A (en) | Mixture of salts and uses of the mixture | |
JP3619921B2 (en) | Bicarbonate solid dialysis agent | |
US3993751A (en) | Process for stabilizing therapeutic compositions and article | |
WO1998010745A1 (en) | Batch quantity dialysate chemical formulations | |
CA2482405C (en) | Multiple compartment bag assembly for dialysis fluid | |
JP5517322B1 (en) | Three-part dialysis agent containing acetic acid and acetate | |
EP1834652A1 (en) | Dialysis preparation | |
EP2513048B1 (en) | Methods for production of high concentration of arginine bicarbonate solution at high pressure | |
JP2000140095A (en) | Solution, its preparation and its preparation system | |
ES2268194T3 (en) | COMBINATION OF AT LEAST TWO INDIVIDUAL DISSOLUTIONS FOR PERITONEAL DIALYSIS AND A TWO CHAMBER BAG CONTAINING SUCH DISSOLUTIONS. | |
JP2000245826A (en) | Neutral peritoneal dialysate | |
JPS5931710A (en) | Drinking solution for supplying calcium | |
EP0084024B1 (en) | Stable supersaturated solutions of sparingly soluble salts | |
EP3508840A1 (en) | Standard reagent kit for dialysis fluid analysis, and aqueous solution for standard reagent, dialysis fluid, and artificial kidney fluid replenishment | |
JP4395995B2 (en) | Preparation for dialysis and method for producing the same | |
RU2568846C2 (en) | Acid dialysis concentrate | |
Frazer et al. | Acidosis and alkalosis: a modern view | |
JPWO2017038099A1 (en) | Standard liquid filler and use thereof | |
JP3271650B2 (en) | Bicarbonate ion-containing aseptic combination liquid preparation or preparation and method for producing the same | |
EP0375885B1 (en) | Aqueous elcatonin solution composition | |
US4301160A (en) | Ready for use, injectable, aqueous solutions of alkali metal salts of canrenoic acid and furosemide and process for their preparation | |
JPH0755823B2 (en) | Vaterite type calcium carbonate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Designated state(s): AT BE CH DE FR GB IT LU NL SE |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: GAMBRO DIALYSATOREN K.G. |
|
17P | Request for examination filed |
Effective date: 19810626 |
|
ITF | It: translation for a ep patent filed | ||
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Designated state(s): AT BE CH DE FR GB IT LI LU NL SE |
|
REF | Corresponds to: |
Ref document number: 3241 Country of ref document: AT Date of ref document: 19830515 Kind code of ref document: T |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 19830531 Year of fee payment: 4 Ref country code: LU Payment date: 19830531 Year of fee payment: 4 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 19830603 Year of fee payment: 4 |
|
REF | Corresponds to: |
Ref document number: 3063088 Country of ref document: DE Date of ref document: 19830616 |
|
ET | Fr: translation filed | ||
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 19830630 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 19830630 Year of fee payment: 4 Ref country code: BE Payment date: 19830630 Year of fee payment: 4 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CH Payment date: 19830704 Year of fee payment: 4 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: DE Payment date: 19830727 Year of fee payment: 4 |
|
PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
26 | Opposition filed |
Opponent name: DETCLEX LIMITED Effective date: 19831202 |
|
PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
PLBI | Opposition filed |
Free format text: ORIGINAL CODE: 0009260 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 19840330 Year of fee payment: 5 |
|
26 | Opposition filed |
Opponent name: FRESENIUS AG Effective date: 19840209 |
|
26 | Opposition filed |
Opponent name: BASF AKTIENGESELLSCHAFT Effective date: 19840210 Opponent name: BOEHRINGER MANNHEIM GMBH Effective date: 19840213 Opponent name: B. BRAUN MELSUNGEN AKTIENGESELLSCHAFT Effective date: 19840210 |
|
26 | Opposition filed |
Opponent name: ORGANO TEKNIKA N.V. Effective date: 19840209 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GB Effective date: 19840606 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Effective date: 19840607 |
|
BERE | Be: lapsed |
Owner name: GAMBRO DIALYSATOREN K.G. Effective date: 19840606 |
|
RDAG | Patent revoked |
Free format text: ORIGINAL CODE: 0009271 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: PATENT REVOKED |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee | ||
NLV4 | Nl: lapsed or anulled due to non-payment of the annual fee | ||
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
27W | Patent revoked |
Effective date: 19840924 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST |
|
EUG | Se: european patent has lapsed |
Ref document number: 80103136.0 Effective date: 19850612 |